We intend to develop a methodology by which the genes coding for disease-specific antigens can be rapidly cloned using recombinant DNA techniques. The system lends itself to high-level expression of these antigens as hybrid proteins, which facilitates production of antibodies to the antigens. With both antigen and antibody, immunodiagnostic tests can be produced for detection of these antigens in clinical samples. This system, encompassing recombinant DNA and immunodiagnostic techniques, can potentially discover large numbers of disease-specific antigens. A spectrum of antigens specific for one disease and tests for them could have considerable diagnostic and therapeutic value. In Phase I, a cDNA library will be constructed from an established human leukemia cell line such as acute lymphoblastic leukemia (ALL). Clones carrying leukemia-specific sequences will be identified by differential screening with probes from normal leukocyte cDNA and probes from ALL cell line-derived cDNA. Cloning will be into the lambda-gtll expression vector. Clones carrying leukemia-specific DNA can be induced, which, with the lambda-gtll system, will lead to expression of substantial amounts of the antigen fused to beta-galactosidase (hybrid proteins). Because of their large size, the proteins can be easily purified and used to raise specific antisera. Phase II will be the characterization of the cloned, expressed antigens and their cognate antibodies. With the specific antisera, histological and immunological tests will be carried out to identify those antigens specific for the ALL cell line. In addition, other cell lines, including different established leukemia cell lines, will be tested for the presence of these antigens. In parallel, diagnostic tests would be developed for these antigens with the goal of using them for clinical diagnostic research. The use of recombinant DNA techniques gives this methodology the power to find substantial numbers of as yet unidentified leukemia-associated antigens. This could lead to discovery of antigens useful in early diagnosis and treatment of a specific leukemia and has the potential of discovering an antigen(s) specific for more than one leukemia. (2)